Interaction of GLP-I and leptin at rat pancreatic B-cells: effects on insulin secretion and signal transduction.
The incretin effect is reduced in NIDDM, although a corresponding attenuation of incretin hormone secretion does not occur. We characterized the direct interaction of GLP-I, an important incretin hormone, and leptin on insulin secretion and signal transduction in B-cells. Leptin inhibited GLP-I stimulated insulin release from the isolated perfused rat pancreas. Both phases of the biphasic insulin secretory response were inhibited. GLP-I receptor binding and GLP-I induced cAMP generation remained unchanged. Leptin reduced the GLP-I mediated increase of cytosolic Ca2+ concentration. It had similar effects on calcium elevations induced by forskolin. The effect was more pronounced during the plateau phase than during the initial peak. These effects could help to explain leptin's inhibitory effects on insulin secretion. The inhibition of GLP-I's insulinotropic effects by leptin may be an interesting aspect in the pathophysiology of NIDDM. The existence of an "adipo-insular axis" is suggested, in which leptin represents a negative feed-back signal from the adipose tissue to the endocrine pancreas.
Fehmann
H C
HC
Department of Medicine, Philipps University of Marburg, Germany.
Bode
H P
HP
Ebert
T
T
Karl
A
A
Göke
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005934:Glucagon / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D020738:Leptin; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D020738:Leptin; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D018027:Receptors, Glucagon; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium